key: cord-008880-cqbsmrpw
authors: Van Ranst, Marc
title: Chandipura virus: an emerging human pathogen?
date: 2004-09-09
journal: Lancet
DOI: 10.1016/s0140-6736(04)16995-x
sha: 
doc_id: 8880
cord_uid: cqbsmrpw

nan

These two trials provide important information on the natural history of node-negative oestrogen-receptor-positive breast cancer, and offer insights into our ability to alter that natural history. Although node-negative patients are often referred to as low risk, it is clear from the 35% relapse rate in the placebo arm of NSABP B-14 that these patients are at significant risk for relapse. In that trial all patients benefited from tamoxifen use regardless of age or menopausal status, which translated into an overall survival benefit that was highest in the youngest cohort of patients. Less clear is which patients warrant chemotherapy in addition to tamoxifen. A survival benefit 5 has been seen with the addition of chemotherapy to tamoxifen in postmenopausal oestrogenreceptor-positive node-positive patients, but it is unclear whether this benefit can be extrapolated to all node-negative patients. NSABP B-20 showed significant benefits in terms of relapse-free survival in all age groups, but this resulted in a significant improvement in overall survival only in the youngest cohort. Clearly the expectations and limitations of chemotherapy must be discussed with patients, especially the elderly, because competing health concerns, such as heart disease, might outweigh the small potential benefit of adjuvant chemotherapy. Standard prognostic criteria, 6 and ongoing work with molecular profiling 7 may identify a subgroup of node-negative patients that has a particularly high risk for relapse and may benefit the most from adjuvant chemotherapy. This molecular profiling, with the current and planned Intergroup and Breast International Group trials, will provide insights into the effectiveness and indications for chemotherapy in node-negative and elderly patients, and is congruent with the statement made by Fisher et al that factors other than age and menopausal status must dictate systemic treatment.

Are these older trials relevant in the era of aromatase inhibitors? Recent adjuvant trials have suggested that aromatase inhibitors are effective both as initial therapy, 8 and after either 2-3 years 9 or 5 years 10 of tamoxifen. Both nodenegative and node-positive patients benefit from these newer hormonal agents, and from the published data, one cannot identify a subgroup that should not be considered for treatment. The latest reports from NSABP provide reassurance about the long-term efficacy of tamoxifen, data that we do not yet have for the newer agents. One benefit of reviewing this follow-up data is a reiteration of the need for long-term follow-up and persistent reporting to ensure that efficacy is maintained and unanticipated toxicities are not uncovered. It is a reminder that cooperative groups are committed to a relentless re-analysis of the data. Adjuvant trials run by pharmaceutical companies must be held to the same standard.

British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 4E6 kgelmon@bccancer.bc.ca

We declare that we have no conflict of interest. Chandipura virus is a member of the Vesiculovirus genus of the family Rhabdoviridae. It was first isolated in 1965, from the blood of two adults with a febrile illness in a village in Nagpur County, Maharashtra State, India. 1 The only other instance when the virus was isolated in human beings was in 1980, in Madhya Pradesh, India, from a patient with acute encephalitis. 2 The likely vector of Chandipura virus is the female phlebotomine sandfly. 3 During the 2003 outbreak, Chandipura virus RNA was detected by PCR in sandflies collected around the house of a patient with encephalitis.

Since 1965, the virus has been reported in three adjoining states in central India: Madhya Pradesh, Maharashtra, and Andhra Pradesh. The virus has probably been endemic in this region for decades, and might have been responsible for several earlier outbreaks of encephalitis that have been recorded in India since 1954. However, the geographical distribution of the virus might extend well beyond India; it has also been detected in sandflies in Senegal and Nigeria. 4, 5 Do not feel too bad if you have never heard of Chandipura virus before. Since the discovery of the virus in 1965, fewer than two articles a year have been published about it. In the year after the outbreak of severe acute respiratory syndrome (SARS) in 2003, more than 1800 articles were published on the SARS coronavirus. I doubt if the Chandipura virus outbreak in central India will be followed by a similar flurry of research activity. In the zoonotic animal virus farm, all viruses are equal, but some viruses are more equal than others. But, part of the explanation for the difference in research interests might be owing to the fact that Koch's postulates were fulfilled for the causal role of a novel coronavirus in the SARS epidemic, but not yet for the association of Chandipura virus with the outbreak of encephalitis in 2003.

The story of the first discovery of the Chandipura virus and its potential role in the 2003 outbreak can not be told without mentioning the National Institute of Virology (NIV) in Pune, India. This institute was established in 1952, under the auspices of the Rockefeller Foundation and the Indian Council of Medical Research, to investigate arthropod-borne viruses. The NIV is currently a WHO Collaborating Centre for arboviruses. Only when regional surveillance networks are closely cooperating with regional reference diagnostic laboratories can they function as effective early-warning beacons for emerging infections. The US Centers for Disease Control and Prevention cannot, and should not, function as the ultimate global reference laboratory. The threshold for sending samples to a small regional laboratory is lower than that for sending it to a far away and often culturally incongruent mammoth laboratory. Strengthening the regional diagnostic laboratory facilities in developing countries is an important global-health priority, and will result in a surveillance net with smaller meshes.

A lot has already been achieved, and the diagnosis of the current outbreak of viral encephalitis is a good example of a sentinel system that worked. However, much more remains to be done: in the infectious disease sphere, there are (and I paraphrase the US Secretary of Defense Donald Rumsfeld slightly out of context here) a lot of "known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns-the ones we don't know we don't know." The 2003 encephalitis outbreak in India taught us that the previously unknown Chandipura virus joins the seemingly ever-growing list of the known important human pathogens. I bet there are still a lot of unknown unknown infectious diseases awaiting us.

Chadipura: a new arbovirus isolated in Ì ndia from patients with febrile illness

Isolation of Chandipura virus from the blood in acute encephalopathy syndrome

Isolation of Chandipura virus from sand flies in Aurangabad

First isolations of arboviruses from Phlebotomine sand flies in West Africa

Oligonucleotide fingerprints of RNA species obtained from rhabdoviruses belonging to the vesicular stomatitis virus subgroup